Synovial joints are the most common joints of the mammalian skeleton. They are highly evolved and movable. A typical synovial joint comprises two bone ends covered by a layer of articular cartilage. The cartilage is smooth and resilient, and facilitates low-friction movement of the bones in the joint. The bone ends and associated cartilage are surrounded by a joint capsule—a “sack” of membrane that produces synovial fluid. The capsule and fluid protect and support the cartilage and connective tissue, carrying nutrients to the articular cartilage and removing the metabolic wastes. The articular cartilage is a thin layer of hyaline cartilage on the epiphysis of the bone with a limited capacity for repair when damaged. Additionally, the natural aging process can cause the articular cartilage to degenerate somewhat, reducing its capacity to protect and cushion the bone ends. As in all synovial joints, where the facets contact each other there is a lining of cartilage lubricated by a thin layer of synovial fluid. The cartilage and synovial fluid decrease friction at the joint, extending joint life and preventing inflammation and associated pain.
Under normal conditions, the body maintains the synovial joint in a state of homeostasis through a variety of complex hormonal and mechanical feedback mechanisms. Two types of insult or injury can upset the delicate homeostatic balance. Repeated trauma or stress (slow chronic insult) to the joint during everyday use, e.g., athletic training or performance, is often the inciting cause of joint inflammation and loss of homeostasis. Initially, such stress results in only soft tissue inflammation in the form of synovitis or capsulitis (e.g., traumatic synovitis). Cartilage damage may or may not initially be present in the early stages of stress related injury or inflammation. However, the release of inflammatory mediators into the joint such as prostaglandins, cytokines, lysosomal enzymes and free radicals can lead to damage of articular cartilage and can cause cartilage degradation and can lead to development of degenerative joint disease (DJD).
A second type of insult or injury, the osteochondral defect, e.g., a chip fracture, is often associated with an acute mechanical failure or traumatic injury, e.g., an acute racing or training injury, although, such a fracture can be due to secondary complications associated with chronic DJD. In this scenario, the lesion often starts as a traumatically induced defect in the articular cartilage. This may occur as a fragmentation of the original tissue from the joint margins or other defect which compromises the surface and integrity of the articular cartilage. Exposure of the supporting subchondral bone to synovial fluid and the intermittent pressures of the synovial fluid generated by repeated joint movement (repeated stress and trauma of training or racing) can lead to progressive subchondral bone sclerosis and eventual dislodging of the chip or bone fragment. Left untreated, the resulting damage often becomes progressive and DJD results.
Joint inflammation may also arise as a consequence of a pathological condition such as rheumatoid arthritis, or non-injuriously as a mere consequence of the degeneration that is part of the natural aging process. For example, the cartilage covering the joint may deteriorate and start to fray. The fraying process may cause pieces of cartilage to break free, and the previously smooth surfaces may become rough. Moreover, the nerves associated with the joint become irritated and inflamed, causing severe pain and restricting movement of the joint.
Once compromised, the damage to articular cartilage is usually permanent. In general, once damaged, therapy is normally directed at limiting or reducing joint inflammation, limiting the release of inflammatory mediators, removal of the inciting cause (e.g., the chip) and replacement of synovial fluid components. These measures are combined with a period of rest to allow for healing and fibrocartilage deposition at the affected area. The long term therapeutic objective is directed at slowing the progression of degenerative processes and controlling the clinical signs of DJD. Prevention is often aimed at limiting joint inflammation before damage to cartilage occurs and in providing proper nutritional support.
Besides cartilage tissue, other tissues release inflammatory cytokines upon injury. Such tissue includes muscles, ligament, tendon, etc. Studies have shown release of inflammatory cytokines not just when these tissues are injured, but also long after the injury.
Clinically, joint inflammation is associated with joint stiffness, pain, weakness, and sometimes joint fatigue. Uniformly, the joint is tender and swollen, and often erythematous. In the United States alone, millions of patients suffer from joint inflammation. Afflicted individuals are frequently disabled, and the costs of medical care for patients suffering from such disorders are significant. While numerous means are available for treatment of joint inflammation, and new treatments continue to become available, none of these is as safe and effective as could be desired. There remains a need for new approaches and better methods to control joint inflammation.